treatment of hemophilia a patients with fviii inhibitors

Conditions: Hemophilia A

Summary: this is a non-interventional, multicenter, observational, international study in male persons with haemophilia a who have developed inhibitors to any replacement coagulation factor viii (fviii) product. the purpose of the study is to capture different approaches in the management of persons with haemophilia a and fviii inhibitors, document current immune tolerance induction approaches, and evaluate the efficacy and safety of immune tolerance induction, including the combination of fviii and emicizumab. patients will be assigned to 1 of 3 groups based on the treatments they receive, and may switch to another group if their treatment is changed. participants will be followed after a maximum observational period of 5 years.

this study will capture different approaches in the management of persons with haemophilia a (ha) and inhibitors. ha is a serious blood coagulation disorder caused by a deficiency in fviii that results in a failure to produce fviii in sufficient quantities to achieve satisfactory haemostasis. patients with ha are predisposed to recurrent bleeds into joints and soft tissues that culminate in debilitating arthropathy and long-term morbidity. ha can be effectively treated with replacement fviii concentrates, obtained by fractionation of human plasma (pdfviii) or using recombinant technology (rfviii). in patients receiving fviii replacement therapy, inhibitors can develop that neutralise the effect of treatment. inhibitors develop in \~35% of patients who have not been previously exposed to fviii treatment and \~1% of patients who have undergone previous fviii treatment. inhibitor development has major adverse implications on bleeding rates, morbidity, mortality and quality of life. immune tolerance induction (iti), which involves prolonged treatment with plasma-derived (pdfviii) or recombinant fviii (rfviii), is the only clinically proven strategy for eradication of inhibitors and is recommended as the primary treatment option in european and us guidelines. bypassing agents (activated recombinant factor vii \[rfviia\] and activated prothrombin complex concentrate \[apcc\]) are used to manage bleeding episodes (bes) and for prophylaxis or in surgical settings in patients with fviii inhibitors. the bispecific factor ix (fix) and factor x (fx) monoclonal antibody emicizumab was approved in the us in november 2017, and in europe in february 2018. the overall objective of this study is to capture different approaches in the management of participants with ha and inhibitors, document current iti approaches, and evaluate efficacy and safety of iti, including the combination of fviii and emicizumab. patients will be assigned to 1 of 3 groups based on the treatments they receive: * group 1 receives iti with nuwiq, octanate, or wilate, with apcc or rfviia administered as needed * group 2 receives iti with nuwiq, octanate, or wilate, in combination with emicizumab, with apcc or rfviia administered as needed * group 3 receives routine prophylaxis with emicizumab, apcc or rfviia without iti

Eligibility criteria:
inclusion criteria: * male persons with haemophilia a, of any severity, who have a historical inhibitor titer ≥ 0.6 bu/ml, including those who have failed previous immune tolerance induction (iti) attempt(s) * persons undergoing iti with nuwiq, octanate, or wilateor undergoing iti with nuwiq®, octanate® or wilate® and receiving prophylactic therapy with emicizumab, activated prothrombin complex concentrate (apcc), or activated recombinant factor vii (rfviia) * participants or participants' parent(s)/legal guardian(s) must be capable of giving signed informed consent and be able to understand the trial documents exclusion criteria: * participants are excluded from the trial if any coagulation disorder other than haemophilia a is diagnosed * partly retrospective patients will be excluded if detailed documentation on treatment, all bleeding episodes, inhibitor titers, and fviii levels is not available for the retrospective period

Keywords: blood disorders